Ethambutol (Myambutol®), 2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol, is an orally administered anti-mycobacterial agent. Ethambutol is commonly prescribed to treat Mycobacterium tuberculosis infections, and is often used in conjunction with either isoniazid or isoniazid plus streptomycin (Chan et al, British Medical Journal 2002, 325, 1282-6). Mycobacterium tuberculosis frequently develops resistance to anti-tuberculosis drugs. Consequently, ethambutol should be combined with at least one other anti-tuberculosis drug. Anti-tuberculous drugs which can be used in combination with ethambutol include: cycloserine, ethionamide, pyrazinamide, viomycin, isoniazid, aminosalicylic acid, streptomycin and other similar drugs. In addition to treating Mycobacterium tuberculosis, ethambutol has shown promise as a therapy in treating other mycobacterial infections, such as Mycobacterium avium complex (Field et al, Chest. 2003, 124, 1482-1486). Further, ethambutol can be used as a chelation therapy agent for heavy metal toxicity, such as saturnism (Dam et al, Vietnam Reveue. Pharmaceutique 1983, 111-118;, J. Otola yngol 2006, 35(2), 117-121; Nguyen et al, Journal of Trace and Microprobe Techniques 1996, 14(1), 153-66).

Ethambutol is administered as its (S,S)-enantiomer, which is 200-500 times more potent than the (R,R)-enantiomer and the meso-isomer (Hausler et al, Bioorg. Med. Chem. Lett. 2001, 11, 1679-81; Stauffer et al, Tetrahedron 2002, 58, 9765-9767).
Recent studies indicate that the primary site of action for ethambutol is the mycobacteria's arabinan biosynthesis, both in arabinogalactan and LAM (Mikusova et al, Antimicrob Agents Chemother 1995, 39, 2484-2489). The mechanism of action for ethambutol is still not known completely, but it probably interferes with the synthesis of proteins and nucleic acids by acting as an anti-metabolite. The Mycobacterium's cell wall is made from mycolic acids covalently linked to the 5′-hydroxyl groups of D-arabinose residues of arabinogalactan, thus forming mycolyl-arabinogalactan-peptidoglycan complexes. By ethambutol filling in as an anti-metabolite, it disrupts the formation of these mycolyl-arabinogalactan-peptidoglycan complexes, which then leads to increased permeability of the cell wall. This effect has been hypothesized to precipitate more facile entry of other antituberculosis drugs. While other anti-tuberculosis drugs are available, ethambutol is considered a “front line drug” and is included in most anti-tuberculosis therapies. Ethambutol, however, can cause optic neuropathy in certain patients (Fraunfelder et al, Expert Opinion on Drug Safety 2006, 5(5), 615-618). The mechanism of action for this toxicity has not been shown with certainty, but it has been suggested that the toxicity of ethambutol and, in particular, its diacid metabolite is due to their abilities to chelate zinc (Heng et al, Invest Ophthalmol Vis Sci. 1999, 40, 190-196).